Apixaban versus enoxaparin for thromboprophylaxis after knee replacement (ADVANCE-2): a randomised double-blind trial
Apixaban versus enoxaparin for thromboprophylaxis after knee replacement (ADVANCE-2): a randomised double-blind trial
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DOI：
10.1016/s0140-6736(09)62125-5
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发表时间：
2010-03-06
期刊：
影响因子：
168.9
通讯作者：
Hornick, Philip
中科院分区：
文献类型：
--
作者：
Lassen, Michael Rud;Raskob, Gary E.;Hornick, Philip
背景 低分子量肝素如依诺肝素是预防大关节置换术后静脉血栓栓塞的首选。阿哌沙班是一种口服活性 Xa 因子抑制剂，可能与依诺肝素一样有效，出血风险较低，并且更容易使用。我们评估了这些药物在选择性全膝关节置换术后的疗效和安全性。 方法 在 ADVANCE-2（一项多中心、随机、双盲 3 期研究）中，接受选择性单侧或双侧全膝关节置换术的患者通过交互式中央电话系统被随机分配接受口服阿哌沙班 2.5 mg 每日两次 (n=1528) 或皮下注射依诺肝素 40 mg 每日一次 (1529)。随机化时间表由百时美施贵宝随机化中心生成，并按研究地点和单侧或双侧手术进行分层，区块大小为四。研究人员、患者、统计学家、裁决者和指导委员会对分配情况不知情。阿哌沙班在伤口闭合后 12-24 小时开始使用，依诺肝素在手术前 12 小时开始使用；两种药物均持续 10-14 天，同时安排双侧上行静脉造影。主要结局是治疗期间无症状和有症状的深静脉血栓形成、非致命性肺栓塞和全因死亡的综合结果。统计计划要求阿哌沙班在检验优效性之前具有非劣效性；分析是按意向治疗进行非劣效性检验。该研究在 ClinicalTrials.gov 上注册，编号为 NCT00452530。结果显示，分配接受治疗的 3057 名患者（1528 名阿哌沙班，1529 名依诺肝素）中的 1973 名患者符合主要疗效分析的条件。 976 名阿哌沙班患者中的 147 名 (15%) 和 997 名依诺肝素患者中的 243 名 (24%) 报告了主要结局（相对风险 0.62 [95% CI 0.51-0.74]；p
Background Low-molecular-weight heparins such as enoxaparin are preferred for prevention of venous thromboembolism after major joint replacement. Apixaban, an orally active factor Xa inhibitor, might be as effective, have lower bleeding risk, and be easier to use than is enoxaparin. We assessed efficacy and safety of these drugs after elective total knee replacement.Methods In ADVANCE-2, a multicentre, randomised, double-blind phase 3 study, patients undergoing elective unilateral or bilateral total knee replacement were randomly allocated through an interactive central telephone system to receive oral apixaban 2.5 mg twice daily (n=1528) or subcutaneous enoxaparin 40 mg once daily (1529). The randomisation schedule was generated by the Bristol-Myers Squibb randomisation centre and stratified by study site and by unilateral or bilateral surgery with a block size of four. Investigators, patients, statisticians, adjudicators, and steering committee were masked to allocation. Apixaban was started 12-24 h after wound closure and enoxaparin 12 h before surgery; both drugs were continued for 10-14 days, when bilateral ascending venography was scheduled. Primary outcome was the composite of asymptomatic and symptomatic deep vein thrombosis, non-fatal pulmonary embolism, and all-cause death during treatment. The statistical plan required non-inferiority of apixaban before testing for superiority; analysis was by intention to treat for non-inferiority testing. The study is registered at ClinicalTrials.gov, number NCT00452530.Findings 1973 of 3057 patients allocated to treatment (1528 apixaban, 1529 enoxaparin) were eligible for primary efficacy analysis. The primary outcome was reported in 147 (15%) of 976 apixaban patients and 243 (24%) of 997 enoxaparin patients (relative risk 0.62 [95% CI 0.51-0.74]; p